CN115337465B - Anti-adhesion membrane material and preparation method thereof - Google Patents

Anti-adhesion membrane material and preparation method thereof Download PDF

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CN115337465B
CN115337465B CN202211269947.3A CN202211269947A CN115337465B CN 115337465 B CN115337465 B CN 115337465B CN 202211269947 A CN202211269947 A CN 202211269947A CN 115337465 B CN115337465 B CN 115337465B
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macromonomer
hydrophilic polymer
degradable polyester
copolymer
membrane material
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CN115337465A (en
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李娟�
石道昆
康亚红
吴艳雪
乔卞卞
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Shanghai Mingyue Medical Technology Co ltd
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Shanghai Mingyue Medical Technology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/042—Polysaccharides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/043—Proteins; Polypeptides; Degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/048—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body

Abstract

The invention relates to an anti-adhesion membrane material and a preparation method thereof, wherein the preparation method comprises the following steps: providing a main raw material for preparing the anti-adhesion membrane material, wherein the main raw material comprises a copolymer macromonomer or at least one of a hydrophilic polymer macromonomer and a degradable polyester macromonomer; or the main raw material comprises a hydrophilic polymer macromonomer and a degradable polyester macromonomer; at least one end of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer has a first reactive group for crosslinking, the first reactive group being selected from one of a carbon-carbon double bond and a carbon-carbon triple bond; and mixing the main raw material and an initiator, carrying out hot die pressing and carrying out cross-linking treatment to obtain the anti-adhesion membrane material.

Description

Anti-adhesion membrane material and preparation method thereof
Technical Field
The invention relates to the technical field of medical materials, in particular to an anti-adhesion membrane material and a preparation method thereof.
Background
Intrauterine adhesion (IUA), also known as Asherman syndrome, is one of the most common uterine diseases in gynecology, and is mostly caused by surgical operations such as artificial light abortion, diagnostic uterine curettage, submucosal myoma removal, uterine polyp removal and the like, which cause damage to the endometrial lining or infection of the uterine cavity, and cause partial or complete adhesion of the uterine cavity or the uterine neck. The patient may have symptoms of hypomenorrhea, amenorrhea, abortion, infertility and the like, and the recovery and the reproductive health of the female after the operation are seriously influenced.
Currently, hysteroscopy intrauterine adhesion separation (TCRA) is the first choice for treating IUA, but the postoperative re-adhesion rate is high. Therefore, how to prevent postoperative re-adhesion becomes the key to successful treatment. The existing clinical preventive measures mainly comprise two types, one is taking estrogen after operation, and the other is placing intrauterine device or air sac ureter after operation or injecting hyaluronic acid gel. The treatment course and the administration dosage of the hormone therapy are still safe. The latter type of therapy employs a physical barrier to block the anterior and posterior walls of the endometrium for the purpose of adhesion prevention, but has certain disadvantages. If the intrauterine device or the ureter is placed in the uterine cavity, the intrauterine device or the ureter needs to be taken out again for operation, so that the burden of the body of a patient is increased; the effective time interval of the anti-adhesion barrier in the uterine cavity is at least 2 weeks, the residence time of the hyaluronic acid gel in the uterine cavity is short, and the better anti-adhesion effect is difficult to play.
The prevention of postoperative adhesion by barrier of absorbable anti-adhesion products is an important means in current clinical application, and mainly comprises the forms of films, gels, injections and the like. The ideal absorbable anti-adhesion product has good biocompatibility, safety, proper degradation period and convenience in use and operation. Some technologies adopt an electrostatic spinning technology and a hot pressing technology to prepare a polyhydroxyalkanoate electrospun membrane, and graft modification is carried out by Polydopamine (PDA), so that the polyhydroxyalkanoate/polydopamine composite electrospun membrane is prepared, and has the characteristics of adhesion prevention, good biocompatibility and excellent mechanical property, but dichloromethane used in the preparation process of the electrospun membrane has high chemical toxicity and potential harm to the environment and workers. Some technologies take chitin fibers and gamma-polyglutamic acid as raw materials to prepare modified hydrogel, and the modified hydrogel is subjected to high-voltage electrostatic spinning and hot pressing treatment to obtain the degradable hemostatic and antibacterial biomedical film, which is short in degradation time and excellent in hemostatic and antibacterial properties, but crab shells and shrimp shells are taken as raw materials, and a final product can be obtained only by preparing the chitin, the chitin fibers, the gamma-polyglutamic acid hydrogel and the chitin/gamma-polyglutamic acid modified hydrogel, so that the preparation period is long, the operation is complex, and the industrial production is not facilitated.
Disclosure of Invention
Therefore, the anti-adhesion film material and the preparation method thereof are needed to be provided, wherein the process is environment-friendly, and the prepared anti-adhesion film material has good compatibility, water absorption rate, excellent mechanical property and flexibility.
The invention is realized through the following technical scheme.
In one aspect of the invention, the invention provides a preparation method of an anti-adhesion membrane material, which comprises the following steps:
providing a main raw material for preparing the anti-adhesion membrane material; the main body raw material comprises a copolymer macromonomer or at least one of a hydrophilic polymer macromonomer and a degradable polyester macromonomer; or the main raw material comprises a hydrophilic polymer macromonomer and a degradable polyester macromonomer; at least one end of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer has a first reactive group for crosslinking, the first reactive group being selected from one of a carbon-carbon double bond and a carbon-carbon triple bond;
and mixing the main raw material and an initiator, carrying out hot die pressing and carrying out cross-linking treatment to obtain the anti-adhesion membrane material.
In some embodiments, the hot pressing temperature is 120 to 250 ℃, the pressure is 0.1 to 8MPa, and the hot pressing time is 3 to 25min.
In some embodiments, the film material obtained by hot die pressing is cooled to 10-35 ℃, the initial cooling temperature is 100-180 ℃, and the cooling rate of the cooling is controlled to be 5-50 ℃/min.
In some embodiments, the cooling rate is controlled to be 10-25 ℃/min.
In some embodiments, the hot die pressing is carried out in a die pressing mold, and gaskets are respectively arranged at the bottom and the top of a forming cavity of the die pressing mold;
the gasket is a metal sheet, a glass sheet or a polymer film; and/or the surface of the gasket facing the molding cavity is provided with a micro-nano concave-convex structure.
In some of these embodiments, the initiator is a thermal initiator, and the crosslinking treatment is performed simultaneously in the thermal compression molding;
or the initiator is a photoinitiator, and ultraviolet irradiation is adopted to carry out crosslinking treatment at the same time of or after the hot die pressing.
In some embodiments, the wavelength of ultraviolet light used for the ultraviolet illumination is 254nm to 400nm, and the energy density of the ultraviolet light is 100 to 1000mW/cm 2 The time of ultraviolet illumination is 5min to 60min; alternatively, the first and second electrodes may be,
when the ultraviolet light is irradiated and the heating treatment is carried out at the same time, the temperature of the heating treatment is 60-150 ℃.
In some embodiments, the membrane obtained by the crosslinking treatment is soaked in a solvent and then dried; the step of soaking in the solvent satisfies at least one of the following conditions a-d:
a. the solvent comprises at least one of water, ethanol, acetone, ethyl acetate, dichloromethane and chloroform;
b. the usage amount of the solvent in the soaking is 30 to 500 times of the mass of the membrane material;
c. the soaking time is from 10min to 12h;
d. the soaking temperature is 10-35 ℃.
In some of these embodiments, the drying step is followed by the steps of:
preheating the film material obtained in the drying step at 30-60 ℃, folding the film material to a target shape, and then cooling and shaping the film material.
In some of these embodiments, the degradable polyester segment units in the copolymer macromonomer or the degradable polyester macromonomer are polymerized from at least one of D, L-lactide, D-lactide, L-lactide, glycolide, epsilon-caprolactone, delta-valerolactone, epsilon-alkyl substituted caprolactone, delta-alkyl substituted valerolactone, orthoesters, butylene succinate, p-dioxanone, and trimethylene carbonate;
and/or the hydrophilic polymer chain segment in the copolymer macromonomer or the hydrophilic polymer macromonomer comprises at least one of polyethylene glycol, polyethylene oxide, polyethylene pyrrolidone, hydrophilic polysaccharide and polypeptide.
In some of these embodiments, the host material further comprises at least one of a linear degradable polyester, a linear hydrophilic polymer, and a linear degradable polyester-hydrophilic polymer copolymer.
In some of the embodiments, the linear degradable polyester and the degradable polyester segment in the linear degradable polyester-hydrophilic polymer copolymer are polymerized from at least one of D, L-lactide, D-lactide, L-lactide, glycolide, epsilon-caprolactone, delta-valerolactone, epsilon-alkyl substituted caprolactone, delta-alkyl substituted valerolactone, orthoester, butylene succinate, p-dioxanone, trimethylene carbonate;
and/or the hydrophilic polymer chain segment in the linear hydrophilic polymer and the linear degradable polyester-hydrophilic polymer copolymer comprises at least one of polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, hydrophilic polysaccharide and polypeptide.
In some embodiments, the main raw material further comprises a hydrophilic monomer having a second active group selected from one of a carbon-carbon double bond and a carbon-carbon triple bond.
In one embodiment, the hydrophilic monomer includes at least one of acrylic acid, acrylamide, vinyl alcohol, and N-vinyl pyrrolidone.
In another aspect of the invention, the invention provides an anti-adhesion membrane material which is prepared by adopting any one of the preparation methods.
According to the preparation method of the anti-adhesion membrane material, the specific type of main raw materials and the initiator are mixed, subjected to hot die pressing and subjected to crosslinking treatment, so that the anti-adhesion membrane material is obtained. The raw materials used in the preparation method are green, nontoxic and environment-friendly, the preparation process is simple to operate, the required period is short, and the prepared anti-adhesion membrane material has a certain crosslinking degree, is rich in excellent mechanical properties and flexibility, can keep a complete shape in the key period of wound healing and anti-adhesion, plays a role in physical barrier, and can be folded and conveyed by a micro-catheter when in use; the hydrogel has good hydrophilicity, can quickly absorb water to expand to be converted into a hydrogel form, has excellent tissue affinity, and can perform self-adaptive filling and isolation according to the shape and the size of a filled cavity in the water absorption expansion process so as to play a good anti-adhesion role; meanwhile, the used raw materials are degradable, have reasonable degradation rate, can be gradually degraded to be discharged out of the body after the wound is healed, and are safe and effective.
The anti-adhesion membrane material is good in safety and effectiveness when used for treating adhesion prevention, and an implant is not required to be taken out in a secondary operation, so that the problems that the secondary operation is taken out to increase the body burden of a patient, the electrostatic spinning processing steps are complicated, chemical reagents are used, the membrane material is toxic and volatile, the environment pollution is caused, and the degradation period of the membrane material is too short or the degradation period is too fast to be beneficial to wound healing are solved. The anti-adhesion membrane material is simple and easy to prepare, low in equipment cost and beneficial to industrial large-scale production.
Detailed Description
In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. It is to be understood that these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
Furthermore, the terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include at least one such feature. In the description of the present invention, "a plurality" means at least two, e.g., two, three, etc., unless explicitly specified otherwise.
One embodiment of the invention provides an anti-adhesion membrane material and a preparation method thereof. The anti-adhesion membrane will be described in detail with reference to the preparation method. The preparation method comprises the following steps S10-S20:
s10, providing a main raw material for preparing the anti-adhesion membrane material. The main raw material comprises a copolymer macromonomer or at least one of a hydrophilic polymer macromonomer and a degradable polyester macromonomer, namely the schemes (1), (3) to (5) described below. Alternatively, the host material comprises a hydrophilic polymer macromonomer and a degradable polyester macromonomer, scheme (2) described below.
In other words, the main raw material has the following five schemes:
(1) The main raw material comprises a copolymer macromonomer;
(2) The main raw materials comprise hydrophilic polymer macromonomer and degradable polyester macromonomer;
(3) The main raw material comprises a copolymer macromonomer and a hydrophilic polymer macromonomer;
(4) The main raw materials comprise copolymer macromonomer and degradable polyester macromonomer;
(5) The main raw materials comprise a copolymer macromonomer, a hydrophilic polymer macromonomer and a degradable polyester macromonomer.
It is understood that the term "macromer" herein refers to a macromer, which has the same meaning in the art.
The copolymer macromonomer is a hydrophilic polymer-degradable polyester copolymer, at least one end of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer is provided with a first active group for crosslinking, and the first active monomer is selected from one of a carbon-carbon double bond and a carbon-carbon triple bond.
And S20, mixing the main raw material with an initiator, carrying out hot-die pressing and carrying out cross-linking treatment to obtain the anti-adhesion membrane material.
In some of the embodiments, in step S20, the initiator is a thermal initiator, and the crosslinking process is performed simultaneously in the thermal compression.
Further, thermal initiators include azo and peroxide species, including but not limited to dibenzoyl peroxide, azobisisobutyronitrile.
In other embodiments, in step S20, the initiator is a photoinitiator, and ultraviolet light is applied to perform the crosslinking treatment simultaneously with or after the hot embossing. Preferably, ultraviolet light is used for the crosslinking treatment after the hot embossing. Therefore, after the film material is molded by hot die pressing and cooling, the photo-crosslinking treatment is carried out, which is beneficial to the stable shape of the film material.
Further, photoinitiators include both cleavage-type and hydrogen abstraction-type photoinitiators, including but not limited to benzoin and derivatives, benzils, alkylphenones, acylphosphorus oxides, benzophenones, thioxanthone photoinitiators. Photoinitiators include, but are not limited to, benzophenone, 2, 4-dihydroxybenzophenone, 4' -bis (dimethylamino) benzophenone, alpha-dimethoxy-alpha-phenylacetophenone.
In some embodiments, the wavelength of ultraviolet light used for ultraviolet illumination is 254nm to 400nm, and the energy density of the ultraviolet light is 100 to 1000mW/cm 2 The time of ultraviolet illumination is 5min to 60min.
Further, heating treatment is carried out while ultraviolet irradiation is carried out, and the temperature of the heating treatment is 60-150 ℃.
In some embodiments, in the step S20, the hot pressing temperature is 120 to 250 ℃, the pressure is 0.1 to 8MPa, and the hot pressing time is 3 to 25min. Therefore, when a thermal initiator is adopted to initiate a crosslinking reaction, the hot pressing time can influence the crosslinking degree to a certain extent, and further influence the degradation period of the anti-adhesion membrane material.
In some of these embodiments, the hot molding is performed in a molding die having gaskets provided at the bottom and top of the molding cavity, respectively. The gasket may also be formed from an opaque metal sheet or polymeric film for hot embossing with a thermal initiator. The spacer may be selected from a clear glass sheet for hot embossing with a photoinitiator to initiate crosslinking by light.
Further, the gasket is preferably a material that is easily released from the mold, such as a polytetrafluoroethylene film or a PET film.
Further, the surface of the gasket intended to come into contact with the molding material, i.e., the surface of the gasket facing the molding cavity, may be treated with a medical grade release agent to facilitate post-molding release.
Further, the surface of the gasket facing the molding cavity is provided with a micro-nano concave-convex structure, such as a dot matrix pattern. So can form corresponding micro-nano concave-convex structure on the surface of the anti-adhesion membrane material, the contact area and contact tightness of the anti-adhesion membrane material and a target tissue can be improved, and better physical isolation and anti-adhesion effects are achieved. Furthermore, the height of the protrusion in the micro-nano concave-convex structure is 100nm to 10 mu m.
In some embodiments, in step S20, after the hot-molding, the molded product obtained by the hot-molding is cooled to 0 ℃ to 35 ℃, for example, room temperature; and simultaneously controlling the cooling rate of the cooling step to be 5-50 ℃/min. The crystallization degree of a hydrophilic polymer chain segment unit or a hydrophilic polymer macromonomer, namely polyethylene glycol (PEG), in the copolymer macromonomer is adjusted by controlling the cooling rate, so that the mechanical property of the anti-adhesion membrane material is controlled. The initial cooling temperature is 100-180 ℃, namely after hot die pressing, the membrane material is cooled to 100-180 ℃ and then cooled at the cooling rate of 5-50 ℃/min. By adopting the mode, the polyethylene glycol in the membrane material forms seed crystals firstly, and then the crystallization degree is controlled by controlling the cooling rate, thereby being more beneficial to controlling the mechanical property. Note that the cooling initiation temperature may be a hot molding temperature.
Further, the cooling rate of the cooling step is controlled to be 10-25 ℃/min.
And S30, soaking the anti-adhesion membrane material obtained after the crosslinking treatment in the step S20 in a solvent, and drying.
In some of the embodiments, in step S30, the solvent includes at least one of water, ethanol, acetone, ethyl acetate, dichloromethane, and chloroform. Thus, unreacted raw materials are removed by the solvent.
Further, the mass of the solvent used in the soaking step is 30 to 500 times of that of the anti-adhesion membrane material.
Furthermore, the soaking time by the solvent is 10min to 12h. Further, the soaking temperature is 10-35 ℃.
In some embodiments, the drying temperature is-40 ℃ to 50 ℃; and controlling the drying to be constant weight. Further, the drying step may be selected from lyophilization or drying under reduced pressure.
The membrane material obtained in the drying step is formed by adopting the main raw materials of the specific types, has excellent mechanical property and good flexibility at room temperature, and is convenient to bend, convey into a human body and convey to a wound position in a uterine cavity, so that the operation difficulty of medical staff is reduced, and the operation convenience degree is improved.
In some embodiments, the drying step is followed by the steps of:
and S40, preheating the film obtained in the drying step in the step S30 at the temperature of 30-60 ℃, folding the film to a target shape, and then cooling and shaping the film. The anti-adhesion membrane material formed in the way is an anti-adhesion membrane material with pre-folding marks, so that a user can fold the anti-adhesion membrane material according to the pre-folding marks, and the anti-adhesion membrane material is folded and arranged in a micro-catheter to be conveyed to a target position through the micro-catheter for use. After reaching the target position, the anti-adhesion membrane absorbs water and automatically unfolds so as to play the role of physical isolation and adhesion prevention.
Further, the temperature for cooling and shaping is between-50 ℃ and 25 ℃.
In step S10, at least one end of the copolymer macromonomer, the hydrophilic polymer macromonomer, and the degradable polyester macromonomer has a first active group for crosslinking. In other words, the above-mentioned copolymer macromonomer, hydrophilic polymer macromonomer and degradable polyester macromonomer are all crosslinkable substances. The cross-linking reaction can be carried out between the copolymer macromonomers, between the hydrophilic polymer macromonomers and the degradable polyester macromonomers and between the degradable polyester macromonomers through the first active group under the action of the initiator to form a cross-linked network structure. Preferably, both ends of the above-mentioned copolymer macromonomer, hydrophilic polymer macromonomer and degradable polyester macromonomer have a first reactive group for crosslinking.
In the embodiment (1), the hydrophilic polymer segment in the copolymer macromonomer can impart excellent water absorption property to the anti-blocking material and property of exhibiting a soft lubricating gel form after water absorption, and the hydrophobic polyester segment in the copolymer macromonomer can impart mechanical strength to the material anti-blocking material portion.
In the embodiment (2), the hydrophilic polymer macromonomer can impart excellent water absorption performance to the anti-blocking material and exhibits a soft lubricating gel-like performance after water absorption, and the degradable polyester macromonomer can impart mechanical strength to the material anti-blocking material portion.
In the scheme (3), the hydrophilic polymer segment in the copolymer macromonomer can endow the anti-blocking material with excellent water absorption performance and soft lubricating gel-like performance after water absorption, the hydrophobic polyester segment in the copolymer macromonomer can endow the material with mechanical strength on the anti-blocking material part, and the hydrophilic polymer macromonomer can endow the anti-blocking material with excellent water absorption performance and soft lubricating gel-like performance after water absorption. Similarly, in schemes (4) and (5), the copolymer macromonomer, the hydrophilic polymer macromonomer, and the degradable polyester macromonomer can also perform the same function.
In some of these embodiments, the anti-blocking material has a gel content of 10 wt.% to 100 wt.%, preferably 30 wt.% to 100 wt.%. By regulating the gel content of the anti-blocking material, namely regulating the crosslinking density of the anti-blocking material, the anti-blocking material can have excellent degradation rate.
In some of these embodiments, the first reactive group is selected from one of a carbon-carbon double bond and a carbon-carbon triple bond. Therefore, the interpenetrating cross-linked network structure can be formed by cross-linking reaction among the copolymer macromonomers, between the hydrophilic polymer macromonomers and the degradable polyester macromonomers and between the degradable polyester macromonomers through the first active group under the action of the initiator. Further, two first active groups are located at both ends of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer. Wherein, a compound containing a first active group and a reactive group, such as a carboxylic acid group, an acid anhydride, a cyanogen group, is added to react with the terminal hydroxyl of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer to form a product with a terminal carbon-carbon double bond or triple bond.
The preparation method of the anti-adhesion membrane material adopts specific types of main raw materials and initiators to be mixed, hot-pressed and subjected to cross-linking treatment, so that the anti-adhesion membrane material is obtained. The raw materials used in the preparation method are green, nontoxic and environment-friendly, the preparation process is simple to operate, the required period is short, and meanwhile, the prepared anti-adhesion membrane material has a certain crosslinking degree, is rich in excellent mechanical properties and flexibility, can keep a complete shape in the key period of wound healing and anti-adhesion, plays a role in physical barrier, and can be folded and conveyed by a micro-catheter when in use; the hydrogel has good hydrophilicity, can quickly absorb water and expand to be converted into a hydrogel form, has excellent tissue affinity, and can perform self-adaptive filling and isolation according to the shape and the size of a filled cavity in the water absorption and expansion process, thereby playing a better anti-adhesion role; meanwhile, the used raw materials are degradable, have reasonable degradation rate, can be gradually degraded to be discharged out of the body after the wound is healed, and are safe and effective.
Therefore, the anti-adhesion membrane material has good safety and effectiveness when used for treating anti-adhesion, the implant does not need to be taken out in a secondary operation, the problem that the secondary operation is taken out to increase the burden of the body of a patient, the problem that the electrostatic spinning processing step is complicated, the chemical reagent is used, toxic and volatile, the environment pollution is caused, and the problem that the wound healing is not facilitated due to the short or too fast degradation period of the product are solved. The anti-adhesion membrane material is simple and easy to prepare, low in equipment cost and beneficial to industrial large-scale production.
The anti-adhesion membrane material can be used for preventing the adhesion of uterine cavity. Applied to uterine cavity operation, avoid secondary taking out, reduce the probability of re-adhesion which probably occurs, and lighten the burden of the body of a patient.
In some embodiments, the tensile strength of the anti-blocking film is 0.2 to 30MPa, and further 1.5 to 30MPa; the elongation at break is 10-1000%, and further 60-1000%. Furthermore, the water contact angle of the anti-adhesion membrane material is less than or equal to 90 degrees, and the hydrophilicity of the anti-adhesion membrane material is good.
The anti-adhesion membrane material has good hydrophilicity, and the water absorption rate in water can reach 50-1000%. Furthermore, the anti-blocking film can adjust the water absorption rate by adjusting the component ratio of the degradable polyester to the hydrophilic polymer.
In some embodiments, the mass fraction of the degradable polyester chain segment unit in the copolymer macromonomer is 20-99%, and the mass fraction of the hydrophilic polymer chain segment unit is 1-80%.
Or in the total mass of the hydrophilic polymer macromonomer and the degradable polyester macromonomer, the mass fraction of the degradable polyester macromonomer is 20-99%, and the mass fraction of the hydrophilic polymer macromonomer is 1-80%. Thus, the mass ratio of the polyester chain segment unit to the polyhydroxy compound chain segment unit is controlled, and the water absorption rate of the anti-adhesion material can be regulated and controlled within a better performance range.
In some of these embodiments, the degradable polyester segment units or degradable polyester macromonomers in the copolymer macromonomers are polymerized from at least one of D, L-lactide, D-lactide, L-lactide, glycolide, epsilon-caprolactone, delta-valerolactone, epsilon-alkyl substituted caprolactone, delta-alkyl substituted valerolactone, orthoesters, butylene succinate, p-dioxanone, and trimethylene carbonate. The polyester chain segment units have degradability, and the anti-adhesion material can have excellent degradation rate by regulating and controlling the composition of the polyester chain segment units, so that the application of the anti-adhesion material is widened.
In some embodiments, the hydrophilic polymer segment units in the copolymer macromonomer, or the hydrophilic polymer macromonomer, comprise at least one of polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, hydrophilic polysaccharide, and polypeptide. Further, hydrophilic polysaccharides include, but are not limited to, hyaluronic acid, cellulose, chitosan. Further, the polypeptide includes amino acids such as lysine.
Further, in a specific example, the hydrophilic polymer segment unit in the copolymer macromonomer is a polyethylene glycol segment unit or a polylysine segment unit.
Further, the hydrophilic polymer macromonomer is polyethylene glycol or hyaluronic acid having a first active group.
In some of these embodiments, the first reactive group and the second reactive group are each independently selected from one of a carbon-carbon double bond and a carbon-carbon triple bond.
In some embodiments, in the schemes (1) to (5), the body material further includes at least one of a linear degradable polyester, a linear hydrophilic polymer, and a copolymer of a linear degradable polyester and a hydrophilic polymer. Wherein the degradable polyester chain segment in the copolymer of the linear degradable polyester and the linear degradable polyester-hydrophilic polymer is polymerized by at least one of D, L-lactide, D-lactide, L-lactide, glycolide, epsilon-caprolactone, delta-valerolactone, epsilon-alkyl substituted caprolactone, delta-alkyl substituted valerolactone, orthoester, butylene succinate, p-dioxanone and trimethylene carbonate. The hydrophilic polymer chain segment in the linear hydrophilic polymer and the linear degradable polyester-hydrophilic polymer copolymer comprises at least one of polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, hydrophilic polysaccharide and polypeptide. Thus, when polymerization reaction occurs, a cross-linked network structure is formed and simultaneously a linear degradable polyester polymer, a linear hydrophilic polymer and/or a linear degradable polyester-hydrophilic polymer copolymer are formed, the linear degradable polyester polymer, the linear hydrophilic polymer and/or the linear degradable polyester-hydrophilic polymer copolymer are inserted into the cross-linked network structure to form a semi-interpenetrating network structure, and the semi-interpenetrating network structure can endow the material with mechanical strength of the anti-adhesion material part. It is understood that the linear polymer does not undergo a crosslinking reaction with the copolymer macromonomer, i.e., it does not participate in the formation of the crosslinked network structure, but rather penetrates the segments of the linear polymer into the crosslinked network structure to form a semi-interpenetrating network structure. The range of the degradable polyester chain segment in the linear degradable polyester and the linear degradable polyester-hydrophilic polymer copolymer is the same as the range of the degradable polyester macromonomer, and details are not repeated here. The hydrophilic polymer chain segment in the linear hydrophilic polymer and the linear degradable polyester-hydrophilic polymer copolymer is the same as the hydrophilic polymer macromonomer in the selection range, and the details are not repeated.
In some embodiments, in schemes (1) to (5), the main raw material further includes a hydrophilic monomer having a second reactive group selected from one of a carbon-carbon double bond and a carbon-carbon triple bond. Besides homopolymerization of the hydrophilic monomer to generate a hydrophilic polymer, the hydrophilic monomer can also react with the first active group on the copolymer macromonomer, the degradable polyester macromonomer and/or the hydrophilic polymer macromonomer through the second active group. By adding the hydrophilic monomer, the material has good hydrophilicity, is converted into a hydrogel form after rapid water absorption expansion, has excellent tissue affinity, and can be adaptively filled and isolated according to the shape and size of a filled cavity in the water absorption expansion process, thereby playing a good anti-adhesion role. Further, the hydrophilic monomer includes, but is not limited to, one or more of acrylic acid, acrylamide, vinyl alcohol, and N-vinyl pyrrolidone.
In the above scheme (1), the copolymer macromonomer includes, but is not limited to, a double-terminal double bond modified PDLLA-PEG block copolymer, a double-terminal double bond modified PDLLA-PLL block copolymer, and a double-terminal double bond modified PLGA-PLL block copolymer.
In the above scheme (2), the hydrophilic polymer macromonomer includes, but is not limited to, PEG modified with double bonds at both ends, hyaluronic acid modified with double bonds at both ends.
In the above-mentioned schemes (2), (4) and (5), the degradable polyester macromonomer includes, but is not limited to, PDLLA modified with double bonds at both ends, PLGA modified with double bonds at both ends.
In order to make the objects, technical solutions and advantages of the present invention more concise and clear, the present invention is described with the following specific embodiments, but the present invention is by no means limited to these embodiments. The following examples are described as preferred embodiments of the present invention, and can be used to describe the present invention, and should not be construed as limiting the scope of the present invention. It should be understood that any modifications, equivalents, and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
In order to better illustrate the invention, the following examples are given to further illustrate the invention. The following are specific examples.
Comparative example 1
Accurately weighing 4g of PDLLA copolymer and 4g of PEG material, adding the PDLLA copolymer and 4g of PEG material into a stainless steel mold with the size of 100mm x 100mm and the thickness of 500 mu m, placing the PTFE membrane on an upper cushion and a lower cushion, placing the PTFE membrane in a hot press heating plate with the temperature of 150 ℃, carrying out hot press molding for 4min under the pressure of 5MPa, cooling to room temperature at the cooling rate of 10 ℃/min, releasing pressure, taking out the mold, carrying out equipment cutting on the membrane according to the target size, preheating and folding the cut membrane at the temperature of 40 ℃, and shaping at the temperature of 20 ℃ to obtain the final uterine cavity anti-adhesion membrane, namely a contrast sample.
Example 1
Accurately weighing 4g of PDLLA (poly (ethylene glycol) diacrylate) material with double-bond modified two ends and 4g of PEGDA (Chinese name: poly (ethylene glycol) diacrylate) material, adding 0.5% (w/w) benzophenone, uniformly mixing, adding into a stainless steel mold with the size of 100mm x 100mm and the thickness of 500 mu m, placing a lower cushion of PTFE film and an upper cushion of transparent glass in a heating plate of a hot press with the temperature of 170 ℃, carrying out hot press molding for 4min under the pressure of 5MPa, reducing the temperature to room temperature at the cooling rate of 10 ℃/min, releasing the pressure and taking out the mold; placing the mold containing the film material on a constant temperature hot stage at 100 deg.C with 200mW/cm 2 Irradiating with 365nm ultraviolet lamp for 10min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 30min, washing with purified water for three times, and drying at room temperature to constant weight; and (3) cutting the membrane material by equipment according to a target size, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain the final uterine cavity anti-adhesion membrane sample 1.
Example 2
Accurately weighing 6g of PDLLA modified by double bonds at two ends and 2g of PEGMA (Chinese name: poly (ethylene glycol) methyl ether acrylate) material, adding 0.5% (w/w) benzophenone, uniformly mixing, adding into a stainless steel mold with the size of 100mm x 100mm and the thickness of 500 mu m, placing a lower cushion of a PTFE film and an upper cushion of transparent glass in a heating plate of a hot press with the temperature of 150 ℃, carrying out hot press molding for 4min under the pressure of 5MPa, cooling to room temperature at the cooling rate of 10 ℃/min, releasing pressure and taking out the mold; placing the mold containing the film material on a constant temperature hot stage at 100 deg.C with 200mW/cm 2 Irradiating with 365nm ultraviolet lamp for 10min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 30min, washing with purified water for three times, and drying at room temperature to constant weight; the film material is pressed according to the eyesAnd (3) cutting equipment according to the standard size, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain the final uterine cavity anti-adhesion membrane sample 2.
Example 3
Accurately weighing 4g of PLGA-PEG-PLGA copolymer (lactide-glycolide-polyethylene glycol copolymer, the mass ratio of PLGA to PEG in the copolymer is 1); the mold containing the film was placed on a thermostatic hot plate at 100 ℃ with 200mW/cm 2 Irradiating with 365nm ultraviolet lamp for 5min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 10min, washing with purified water for three times, and drying at room temperature to constant weight; and (3) cutting the membrane material by equipment according to a target size, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain a final uterine cavity anti-adhesion membrane sample 3.
Examples 4 to 6
It is basically the same as example 3 except that the temperature reduction rate in the step of reducing the temperature to room temperature after hot press molding at 5MPa for 4min was adjusted from 10 ℃/min in example 3 to that shown in table 1; samples 4 to 6 were obtained accordingly.
Example 7
Accurately weighing 8g of PLGA-PEG-PLGA copolymer (lactide-glycolide-polyethylene glycol copolymer, wherein the mass ratio of PLGA to PEG in the copolymer is 1; placing a mould containing the membrane materialOn a constant temperature heating table at 100 ℃, the temperature is controlled by 200mW/cm 2 Irradiating with 365nm ultraviolet lamp for 5min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 10min, washing with purified water for three times, and drying at room temperature to constant weight; and (3) cutting the membrane material by equipment according to a target size, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain a final uterine cavity anti-adhesion membrane sample 7.
Example 8
Accurately weighing 8g of PLGA-PEG-PLGA copolymer (lactide-glycolide-polyethylene glycol copolymer, the mass ratio of PLGA to PEG in the copolymer is 2; the mold containing the film was placed on a thermostatic hot plate at 100 ℃ with 200mW/cm 2 Irradiating with 365nm ultraviolet lamp for 5min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 10min, washing with purified water for three times, and drying at room temperature to constant weight; and (3) cutting the membrane material by equipment according to a target size, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain a final uterine cavity anti-adhesion membrane sample 8.
Examples 9 to 10
It is basically the same as example 3 except that the hot press molding parameters were adjusted as shown in table 1; samples 9 to 10 were obtained accordingly.
Example 11
Accurately weighing 4g of PLGA-PEG-PLG and 4g of PEGDA material, adding 0.5% (w/w) benzophenone, uniformly mixing, adding into a stainless steel mold with the size of 100mm x 100mm and the thickness of 500 mu m, placing the stainless steel mold into a heating plate of a hot press with the temperature of 150 ℃, hot-pressing and molding for 4min under the pressure of 5MPa, cooling to room temperature at the cooling rate of 10 ℃/min, releasing pressure and taking out the mold; will contain a filmThe mould of the material is placed on a constant temperature hot bench at 100 ℃ and 200mW/cm is used 2 Irradiating with 365nm ultraviolet lamp for 10min, standing at room temperature to room temperature, taking out the membrane material, soaking in 75% alcohol for 30min, washing with purified water for three times, and drying at room temperature to constant weight; and (3) cutting the membrane material according to a target size by using equipment, preheating the cut membrane material at 40 ℃, folding, and shaping at 20 ℃ to obtain a final uterine cavity anti-adhesion membrane sample 11.
Examples 12 to 13
Example 12 was substantially the same as example 13 except that the reaction raw materials were different, specifically, see tables 1 and 2, to obtain sample 12 and sample 13.
The following are performance tests.
Water absorption test: weighing the above uterine cavity anti-adhesion membrane samples by a certain weight, and recording the weight as m 1 Soaking a sample in purified water with the weight more than 10 times of the weight of the sample, taking out the sample after soaking for 24 hours, wiping off the moisture on the surface of the sample by using a dust-free cloth, weighing the sample, and recording the weight as m 2 Water absorption = (m) 2 -m 1 ）/m 1 *100%。
And (3) testing the gel content: weighing the above uterine cavity anti-adhesion membrane samples by a certain weight, and recording the weight as m 3 Soaking the sample in sufficient good solvent for 24 hr, filtering, drying the undissolved sample at normal temperature to constant weight, and recording as m 4 Water absorption = m 4 /m 3 *100%。
And (3) bending evaluation: a uterine cavity anti-adhesion membrane sample with a fixed size is cut, the sample is folded in half at 180 degrees for three times, and whether cracks are generated at the folded position is evaluated.
Tensile strength:
cutting a uterine cavity anti-adhesion membrane sample with a fixed size, soaking the sample in purified water with the weight more than 10 times that of the sample, taking out the sample after soaking for 2 hours, measuring the cross section area of the membrane material after swelling, setting stretching parameters such as stretching speed, initial length, membrane material size and the like in a universal tensile testing machine, starting a tensile test, and recording the tensile strength when the tensile reaches the yield point.
Elongation at break test: cutting a uterine cavity anti-adhesion membrane sample with a fixed size, and soaking the sample in the sampleSoaking in purified water with weight more than 10 times of the membrane material for 2 hr, taking out, measuring the dimension of the membrane material after swelling, and recording the length as L 1 Stretching the film material at a constant speed along the length direction at a set speed, recording the breaking length of the film material as L 2 Elongation at break = (L) 2 -L 1 ）/L 1 *100%。
The test results are shown in tables 1 and 2 below:
TABLE 1
Figure 584837DEST_PATH_IMAGE002
TABLE 2
Figure 545840DEST_PATH_IMAGE004
The non-crosslinked uterine cavity anti-adhesion membrane prepared in comparative example 1 had a low elongation at break and was easily broken upon bending and transportation.
In the embodiments 1 to 13, the cross-linked intrauterine anti-adhesion membrane is prepared by introducing the cross-linkable group, and has obvious advantages in tensile strength, bending property and elongation at break on the basis that the water absorption performance can be basically maintained.
Compared with the comparative example 1, in the example 1, cross-linkable groups (double bonds) are introduced into two ends of one PDLLA of the raw materials in the comparative example 1 to form a partial cross-linked network, double bonds are introduced into the other PEG raw material to further polymerize the other PEG raw material to form a linear polymer, and the linear polymer penetrates into the cross-linked network to form a semi-interpenetrating network structure, so that the water absorption rate can be maintained, and the elongation at break is improved.
Compared with example 1, the proportion of the hydrophilic component PEGMA is reduced in example 2, the water absorption rate of the prepared membrane is reduced, and the tensile strength is improved.
Compared with the examples 1 to 2, the hydrophilic PEG part is introduced into the polyester part in the example 3, so that the prepared uterine cavity anti-adhesion membrane has higher water absorption rate, and the gel content and the elongation at break are kept stable.
As can be seen from examples 3 to 6, the differences are only: controlling different cooling rates after hot press forming, wherein the cooling rate is 5 to 50 ℃/min, and the bending performance, the water absorption performance, the tensile strength and the elongation at break of the composite material are better; further preferably, the cooling rate is 10 to 50 ℃/min, and the water absorption performance, the tensile strength and the elongation at break are better.
Compared with the embodiment 3, PEGMA is omitted in the embodiments 7 to 8, and the embodiments 7 to 8 only differ in the mass ratio of PLGA to PEG in the PLGA-PEG copolymer modified by double bonds at two ends, the anti-adhesion membrane for the uterine cavity prepared in the embodiments 7 to 8 can achieve higher water absorption rate, and the bending performance and the elongation at break are kept stable.
Compared with example 7, the mass ratio of PLGA to PEG in the PLGA-PEG copolymer modified by double bonds at two ends in example 8 is increased, the water absorption of the prepared anti-adhesion membrane for uterine cavity is reduced, and the gel content and the bending performance are kept stable.
As can be seen from comparison among examples 3, 9 to 10, the water-absorbing resin composition has significant advantages in tensile strength, bending properties and elongation at break, while the water-absorbing property is substantially maintained, as compared with comparative example 1. Preferably, the hot press forming parameters of embodiment 3 are preferred.
All possible combinations of the technical features of the above embodiments may not be described for the sake of brevity, but should be considered as within the scope of the present disclosure as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent should be subject to the appended claims, and the description can be used to interpret the contents of the claims.

Claims (13)

1. The preparation method of the anti-adhesion membrane material is characterized by comprising the following steps:
providing a main raw material for preparing the anti-adhesion membrane material; the main raw material comprises a copolymer macromonomer or at least one of a hydrophilic polymer macromonomer and a degradable polyester macromonomer; or the main raw material comprises a hydrophilic polymer macromonomer and a degradable polyester macromonomer; at least one end of the copolymer macromonomer, the hydrophilic polymer macromonomer and the degradable polyester macromonomer is provided with a first active group for crosslinking, wherein the first active group is selected from one of a carbon-carbon double bond and a carbon-carbon triple bond; the degradable polyester chain segment unit in the copolymer macromonomer or the degradable polyester macromonomer is formed by polymerizing at least one of D, L-lactide, D-lactide, L-lactide, glycolide, epsilon-caprolactone, delta-valerolactone, epsilon-alkyl substituted caprolactone, delta-alkyl substituted valerolactone, orthoester, butylene succinate, p-dioxanone and trimethylene carbonate; the hydrophilic polymer chain segment in the copolymer macromonomer or the hydrophilic polymer macromonomer comprises at least one of polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, hydrophilic polysaccharide and polypeptide;
mixing the main raw material and an initiator, carrying out hot die pressing at the temperature of 120-250 ℃, the pressure of 0.1-8MPa and the hot pressing time of 3-25min, and carrying out cross-linking treatment to obtain an anti-adhesion membrane material;
and cooling the membrane material obtained by hot die pressing to 10-35 ℃, wherein the initial cooling temperature is the temperature of the hot die pressing, and the cooling rate of the cooling is controlled to be 5-50 ℃/min.
2. The method of claim 1, wherein the initial temperature of the cooling is 100 ℃ to 180 ℃, and the cooling rate of the cooling is controlled to be 5 ℃/min to 50 ℃/min.
3. The preparation method according to claim 1, wherein the cooling rate is controlled to be 10 ℃/min to 25 ℃/min.
4. The production method according to claim 1, wherein the hot molding is performed in a molding die provided with gaskets at the bottom and the top of a molding cavity of the molding die, respectively;
the gasket is a metal sheet, a glass sheet or a polymer film; and/or the surface of the gasket facing the molding cavity is provided with a micro-nano concave-convex structure.
5. The production method according to claim 1, wherein the initiator is a thermal initiator, and the crosslinking treatment is performed simultaneously in the thermal compression molding;
or the initiator is a photoinitiator, and ultraviolet light is adopted for crosslinking treatment at the same time of or after the hot embossing.
6. The method according to claim 5, wherein the wavelength of the ultraviolet light used for the ultraviolet light irradiation is 254nm to 400nm, and the energy density of the ultraviolet light is 100 to 1000mW/cm 2 The ultraviolet illumination time is 5min to 60min; alternatively, the first and second electrodes may be,
when the ultraviolet irradiation is performed and the heating treatment is performed at the same time, the heating treatment temperature is 60-150 ℃.
7. The production method according to claim 1, wherein the film obtained by the crosslinking treatment is dried after being immersed in a solvent; the step of soaking in the solvent satisfies at least one of the following conditions a-d:
a. the solvent comprises at least one of water, ethanol, acetone, ethyl acetate, dichloromethane and chloroform;
b. the using amount of the solvent in the soaking is 30 to 500 times of the mass of the membrane material;
c. the soaking time is from 10min to 12h;
d. the soaking temperature is 10-35 ℃.
8. The method of claim 7, further comprising, after the step of drying, the steps of:
preheating the film material obtained in the drying step at 30-60 ℃, folding the film material into a target shape, and then cooling and shaping the film material.
9. The method of any one of claims 1 to 8, wherein the host material further comprises at least one of a linear degradable polyester, a linear hydrophilic polymer, and a linear degradable polyester-hydrophilic polymer copolymer.
10. The method according to claim 9, wherein the degradable polyester segment in the linear degradable polyester and the linear degradable polyester-hydrophilic polymer copolymer is polymerized from at least one of D, L-lactide, D-lactide, L-lactide, glycolide, e-caprolactone, δ -valerolactone, e-alkyl substituted caprolactone, δ -alkyl substituted valerolactone, orthoester, butylene succinate, p-dioxanone, trimethylene carbonate;
and/or the hydrophilic polymer chain segment in the linear hydrophilic polymer and the linear degradable polyester-hydrophilic polymer copolymer comprises at least one of polyethylene glycol, polyethylene oxide, polyvinylpyrrolidone, hydrophilic polysaccharide and polypeptide.
11. The method according to any one of claims 1 to 8, wherein the main raw material further comprises a hydrophilic monomer having a second reactive group selected from one of a carbon-carbon double bond and a carbon-carbon triple bond.
12. The method of claim 11, wherein the hydrophilic monomer comprises at least one of acrylic acid, acrylamide, vinyl alcohol, and N-vinyl pyrrolidone.
13. An anti-blocking film material, characterized by being prepared by the preparation method of any one of claims 1 to 12.
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